Effect of sinusoidal electrical cortical stimulation on brain cells

ABSTRACT Background Electrical cortical stimulation is often used in patients with neurological disorders but it is unclear how it modulates different types of brain cells. Objective The aim of this study was to determine the effect of sinusoidal electrical brain stimulation (SEBS) on different types of brain cells and to identify the exact types of brain cells that are stimulated. Methods The study subjects were 40 male Sprague Dawley rats (weight 300–350 g; age 9 weeks). SEBS was delivered continuously at frequencies of 20, 40, 60, or 100 Hz to the sensory parietal cortex using epidurally placed electrodes for 1 week. Transverse rat brain tissue sections were immunolabeled with calmodulin-dependent protein kinase II and parvalbumin (PV) antibodies and with c-Fos for counting of activated excitatory and inhibitory neurons. Computer simulation was performed to cross-validate the frequency-specific cell stimulation results. Results Inhibitory neurons were more excited than excitatory neurons after epidural EBS. Most excitatory neural activity was evoked at 40 Hz ( p <0.05) and most inhibitory neuronal activity was evoked at 20 Hz ( p <0.01). The contralateral sensory cortex was activated significantly more at 40 Hz ( p <0.05) and the corticothalamic circuit at 20 Hz ( p <0.001). Stimulation-induced excitatory and inhibitory neuronal activation was widest at 20 Hz. Conclusions Epidural electrical stimulation targets both excitatory and inhibitory neurons and the related neural circuits. Further exploration is needed to identify circuits that promote the plasticity needed for recovery in patients with specific neurological diseases. Graphical Abstract